A neural basis for antagonistic control of feeding and compulsive behaviors

Leandra R. Mangieri, Yungang Lu, Yuanzhong Xu, Ryan M. Cassidy, Yong Xu, Benjamin R. Arenkiel and Qingchun Tong ()
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Leandra R. Mangieri: University of Texas Health Science Center at Houston
Yungang Lu: University of Texas Health Science Center at Houston
Yuanzhong Xu: University of Texas Health Science Center at Houston
Ryan M. Cassidy: University of Texas Health Science Center at Houston
Yong Xu: Baylor College of Medicine
Benjamin R. Arenkiel: Baylor College of Medicine
Qingchun Tong: University of Texas Health Science Center at Houston

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Abnormal feeding often co-exists with compulsive behaviors, but the underlying neural basis remains unknown. Excessive self-grooming in rodents is associated with compulsivity. Here, we show that optogenetically manipulating the activity of lateral hypothalamus (LH) projections targeting the paraventricular hypothalamus (PVH) differentially promotes either feeding or repetitive self-grooming. Whereas selective activation of GABAergic LH→PVH inputs induces feeding, activation of glutamatergic inputs promotes self-grooming. Strikingly, targeted stimulation of GABAergic LH→PVH leads to rapid and reversible transitions to feeding from induced intense self-grooming, while activating glutamatergic LH→PVH or PVH neurons causes rapid and reversible transitions to self-grooming from voracious feeding induced by fasting. Further, specific inhibition of either LH→PVH GABAergic action or PVH neurons reduces self-grooming induced by stress. Thus, we have uncovered a parallel LH→PVH projection circuit for antagonistic control of feeding and self-grooming through dynamic modulation of PVH neuron activity, revealing a common neural pathway that underlies feeding and compulsive behaviors.

Date: 2018
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DOI: 10.1038/s41467-017-02534-9

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